Staffan Strömblad

The tissue stiffens in cancer mainly due to increased deposition and cross-linking of the extracellular matrix. Based on our unexpected recent findings, we aim to define a protective role for matrix stiffening in cancer development through facilitating the senescence barrier to cancer. This challenges the prevailing dogma that tissue stiffening solely promotes cancer and will fuse two distinct fundamental mechanisms, matrix stiffening and cellular senescence, currently considered separate processes.The applicant leads the project aided by two postdocs and one bioinformatician, and by leading national and international collaborators.Year 1-2 will define the role of matrix stiffness in senescence, using a range of cancer-related senescence induction models in vitro and in vivo where we vary the matrix stiffness. Year 3-5 will complete defining molecular mechanisms for stiffness promotion of senescence, based on in vitro RNAi screening, spatial transcriptomics, and CRISPR-Cas9 gene perturbation in a mouse lung cancer model, as well as characterization of patient samples of pre-invasive breast lesions.This project will advance our fundamental understanding of cancer development and provide vulnerabilities to be explored for cancer diagnosis and treatment. Here, we will explore pre-invasive breast lesions for prediction of patient risk for breast cancer. The project is also relevant to development, aging, fibrosis, cardiovascular disease, cell reprograming and tissue repair.

Swept lasers have enabled paradigm-shifts in biomedical imaging and diagnostics. The SWEEPICS project will research and develop the next generation of swept source lasers with flexible pulse modulation capability, high power output, multi-wavelength coherent output and multi-application potential. SWEEPICS will develop new laser-based systems: a high-speed, high resolution multiphoton high content screening system, a multimodal non-invasive imaging system based on high-speed photoacoustics and multiphoton microscopy, and a smart microscope for accelerated acquisition&diagnostics. The inter-disciplinary consortium of European partners will showcase the SWEEPICS technology in cutting-edge use cases based on novel vascular organoids for animal-free drug-testing and infection studies. This disruptive SWEEPICS technology will rapidly generate high-resolution diagnostic imaging in three-dimension, where the high imaging depth permits penetrating millimeter deep into tissue-like organoids and imaging at high temporal and spatial resolution in order to allow for a drastic reduction of animal testing and increased speed of diagnostic results. It will allow the study of dynamic processes in real-time and at multiple length scales, enabling researchers to observe how cells and tissues respond to viral infections or pathogen-induced inflammation, while also permitting a high-throughput enabled discovery of novel diagnostic biomarkers. Overall, this technology represents a major breakthrough in capable laser technology for high accuracy and throughput medical diagnostics and is poised to make significant contributions to the European laser and biomedical technology landscape.